Intravascular device and method for axially stretching blood vessels

ABSTRACT

Intravascular devices and methods are provided for forming a vascular graft by axially distending a blood vessel to induce growth. These devices advantageously can be implanted via a catheter, thereby eliminating the need for a more invasive implantation procedure when the stretching is to be done in vivo. Preferably, the device for axially distending a blood vessel to induce growth of the vessel includes an intravascular stretching mechanism attachable directly to an interior lumen portion of the blood vessel, and a means for operating the stretching mechanism to cause the vessel to distend axially. The stretching mechanism can include a pair of wires or stents that engage the blood vessel wall. Components of the stretching mechanism can include a shape memory material.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] Priority is claimed to U.S. provisional application No.60/274,703, filed Mar. 9, 2001.

BACKGROUND OF THE INVENTION

[0002] The present invention is generally in the area of methods anddevices for producing vascular tissue grafts from living vasculartissue, and particularly for making autologous grafts.

[0003] Vascular grafts are commonly used by surgeons to bypassobstructions to blood flow caused by the presence of atheroscleroticplaques. Vascular grafts also are used in other applications such asproviding arterial-venous shunts in dialysis patients, vascular repairor replacement and treating aneurysms. Grafts for bypass are often, butnot exclusively, used in the coronary arteries, the arteries that supplyblood to the heart.

[0004] The materials used to construct a vascular graft usually areeither synthetic or of biological origin, but combinations of syntheticand biological materials are under development. The most widely usedbiological vascular grafts are autologous saphenous vein or mammaryartery. Some common synthetic grafts are made of polytetrafluoroethylene(PTFE) (e.g., GORTEX™) or polyester (e.g., DACRON™). Autologous graftshave generally been used more successfully than synthetic grafts.Autologous grafts remain patent (functional) much longer than syntheticgrafts, and saphenous veins often fail in less than five years. Theshort lifetime of synthetic grafts is especially evident with smalldiameter (less than 7 mm diameter) grafts, as most small diametersynthetic grafts occlude within one to two years or less.

[0005] Small diameter vascular grafts are particularly used in coronaryartery bypass surgery. Internal mammary artery (IMA) is the autologousgraft of choice, because it typically has a longer life than venousgrafts (95% patent at five years versus 85% patent at two years).Mammary arterial tissue, however, is difficult to harvest, is typicallynot available in lengths sufficient for multiple bypasses, and itsremoval can result in problems such as problematic wound healing.Moreover, obtaining sufficient venous tissue for repairing an occludedartery can be problematic in patients with venous conditions such asvaricose veins and especially in second or third surgeries in the samepatient. Literature also suggests that IMA used in bypass procedureseither fails soon after transplantation or remains patent indefinitely.See, e.g., Bergsma, et al., Circulation 97(24):2402-05 (1998); Cooley,Circulation 97(24):2384-85 (1998).

[0006] Other arteries such as the gastroepipolic, gastric, radial, andsplenic also are used in coronary bypass procedures. In some cases,autologous or homologous saphenous vein preserved by freezing or otherprocesses is used. A recent American Heart Association/American Collegeof Cardiology consensus document strongly recommends a move to totalarterial revascularization (Eagle, et al. “ACC/AHA Guidelines forcoronary artery bypass graft surgery: A report of the American Collegeof Cardiology/American Heart Association Task Force on PracticeGuidelines”, Committee to Revise the 1991 Guidelines for Coronary ArteryBypass Graft Surgery, American College of Cardiology/American HeartAssociation, J. Am. Coll. Cardiol., 34(4):1262-347 (1999)).

[0007] Development of a longer lasting small-diameter vascular graft isthe subject of much academic and industrial research. One currentapproach is to combine cell culture and biomaterials technologies tomake a living, “tissue engineered” graft. This effort, however, ishindered by the requirements of a successful graft. The graft should beself-repairing, non-immunogenic, nontoxic, and non-thrombogenic; shouldhave a compliance comparable to the artery being repaired; should beeasily sutured by a surgeon; and should not require any specialtechniques or handling procedures. Grafts having these characteristicsare difficult to achieve. Despite the substantial effort to date and thepotential for significant financial reward, academic and industrialinvestigators have failed to produce graft materials that havedemonstrated efficacy in human testing.

[0008] Efforts to avoid or minimize the need for vascular grafts forrepair of otherwise healthy vascular tissue have been described. Forexample, Ruiz-Razura et al., J. Reconstructive Microsurgery,10(6):367-73 (1994) and Stark et al., Plastic & Reconstructive Surgery,80(4):570-78 (1987) disclose the use of a round microvascular tissueexpander for acute arterial elongation to examine the effects on thetissue of such acute hyperextension. The expander is a silicone balloonthat is placed under the vessel to be elongated. The balloon is filledwith saline over a very short period, causing acute stretching andelongation of the vessel. The method is purported to be effective forclosure of arterial defects up to 30 mm without the need for a veingraft. These techniques are appropriate for trauma, but are not used forrestoring blood flow in vessels that are occluded, for example bydisease, which are treated by surgically bypassing the obstruction witha graft. The disclosed methods and devices fail to provide an autologousgraft or versatile substitute. Moreover, the acute stretching may damagethe vessel.

[0009] It has been demonstrated, however, that axial stretching canincrease smooth muscle cell proliferation in an intact blood vessel,thereby substantially enhancing blood vessel growth. See Conklin,“Viability of Porcine Common Carotid Arteries in a Novel Organ CultureSystem” MS Thesis, Georgia Institute of Technology, 1997); Han, et al.,“Axial Stretch Increases Cell Proliferation in Arteries in OrganCulture”, Advances in Bioengineering, ASME BED 48:63-64 (2000).

[0010] PCT WO 99/60952 to Georgia Tech Research Corporation and U.S.Pat. No. 6,322,553 to Vito describe devices and methods for producingaxial growth by mechanically stimulating a blood vessel using axialdistention. These devices anchor to exterior surfaces of the bloodvessels, and consequently their use in vivo is necessarily invasive, atleast requiring endoscopic surgery. The size of the devices also maylimit the sites that are suitable for implantation. It would beadvantageous to develop devices and methods that are less invasive andmore easily installed and used in vivo. It would also be tremendouslybeneficial to the patient to be able to eliminate the need for surgerybefore removal of the grown blood vessel for use as an autologous graft.

[0011] It is therefore an object of the present invention to provideminimally- or non-invasive devices and methods for stretching andgrowing blood vessels in vivo.

[0012] It is another object of the present invention to provide simpledevices and methods for creating natural blood vessel suitable forgrafting.

[0013] It is a further object of the present invention to providedevices and methods for making an autologous blood vessel graft withfewer surgeries.

[0014] These and other objects, features, and advantages of the presentinvention will become apparent upon review of the following detaileddescription of the invention taken in conjunction with the drawings andthe appended claims.

SUMMARY OF THE INVENTION

[0015] Intravascular devices and methods are provided for forming avascular graft by axially distending a blood vessel to stimulate vesselgrowth. These devices advantageously can be implanted via a catheter,thereby eliminating the need for a more invasive implantation procedurewhen the stretching is to be done in vivo. Where the vessel donor is therecipient of the graft, a totally autologous, living vascular graft isprovided.

[0016] The device for axially distending a blood vessel to induce growthof the vessel includes an intravascular stretching mechanism attachabledirectly to an interior lumen portion of the blood vessel, and a meansfor operating the stretching mechanism to cause the vessel to distendaxially. In a preferred embodiment, the intravascular stretchingmechanism is composed of an anchoring wire and a stretching wire,wherein the distal end portions of these wires are separately anchorableto the interior lumen portion at positions axially remote from oneanother. The device may further include a catheter having at least twolumens that are suitable for delivering the stretching wire and theanchor wire into the interior lumen portion of the blood vessel. Thecatheter and wires can be provided as a kit or an assembled device.

[0017] The distal end portion of the anchoring wire, the distal endportion of the stretching wire, or both, can include or be formed of ashape memory material. Preferably, the shape memory material comprisesnickel-titanium or a shape memory polymer. In operation of such anembodiment, the shape memory material changes shape in response to aneffective temperature change, such as the temperature increaseexperienced following insertion of the material into a live mammalianbody. The shape change, for example, can cause the distal end portion ofthe stretching wire to change from a substantially straight form into aspiral configuration which frictionally engages a first position in theinterior lumen portion of the blood vessel and then can cause the distalend portion of the anchoring wire to change from a substantiallystraight form into a spiral configuration which engages a secondposition in the interior lumen portion of the blood vessel. Stretchingforces can then be applied to the wire(s) to push/pull the distalportions away from each other.

[0018] In one variation, the stretching wire can further include anintermediary portion which changes shape, for example by use of a shapememory material, from a substantially straight form into a helicalconfiguration which functions as a compression spring to impart thestretching forces.

[0019] The means for operating the stretching mechanism can include aprime mover that is mechanically, electromechanically, or hydraulicallydriven. This operating means can cause the axial stretching force to beapplied to the vessel in a continuous, intermittent, or cyclical manner,and applied rectilinearly, curvilinearly, or in a combination thereof.The device can also include a controller for controlling the means foroperating the stretching mechanism.

[0020] In another preferred embodiment, the intravascular stretchingmechanism comprises a first stent, a second stent, and a compressionspring operably connected to the first stent and the second stent,wherein the first and second stents are separately anchorable to theinterior lumen portion at positions axially remote from one another. Inthis embodiment, the first stent, the second stent, the compressionspring, or a combination thereof, can include a shape memory material,such as a nickel-titanium alloy or a shape memory polymer.

[0021] In any of these embodiments, the intravascular stretchingmechanism, or a portion thereof, can include a therapeutic orprophylactic agent, such as a growth-stimulating agent, which can bereleased in an effective amount to enhance growth of the blood vessel.Another example is an anti-throbotic agent to minimize the risk of ablood clot during the stretching process. The therapeutic orprophylactic agent can be impregnated in or coated onto the devicecomponents, and/or added and released through a lumen in the catheterthat delivers the device to its intravascular position.

[0022] Methods are provided for distending a blood vessel of a human oranimal to induce blood vessel growth. The steps include (i) insertinginto an interior lumen portion of a blood vessel the stretchingmechanism of the devices described herein; (ii) anchoring the stretchingmechanism to the interior lumen portion at at least two positions whichare axially remote from one another; and (iii) operating the stretchingmechanism to axially stretch the blood vessel between said at least twopositions over a period of time effective to induce axial growth of theblood vessel. This operation step could be active (e.g., applying anexternal force to the mechanism or a component thereof) or passive(e.g., simply releasing an elastic force, such as a spring). Thestretching can be performed in vivo or in vitro in a medium for cellgrowth.

[0023] Methods are also provided for forming a vascular graft for ahuman patient in need thereof. The methods include the steps ofdistending a donor blood vessel by use of one of the intravascularstretching devices and methods described herein, and then excising aportion of the distended donor vessel, that portion thereby providing avascular graft. While a variety of blood vessel types could be stretchedas described herein, the blood vessel preferably is selected from aninternal mammary artery, a femoral artery, a gastroepipolic artery, agastric artery, a radial artery, and a splenic artery, when stretchingthe vessel to form a vascular graft.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024]FIG. 1 is a perspective view of the parts of one embodiment of theintravascular device, which includes a multi-lumen catheter, an anchorwire, and stretching wire.

[0025]FIG. 2 is a perspective view of a wire having a distal end portioncomprising a shape memory material in a straight configuration (FIG. 2A)and in a spiral configuration (FIG. 2B).

[0026] FIGS. 3A-E are partial cross-sectional views of a blood vessel inwhich one embodiment of the intravascular device is being deployed andoperated to stretch the blood vessel, using external force to push ananchored stretching wire away from an anchor wire.

[0027]FIG. 4 is a perspective view of a wire having a distal end portioncomprising a shape memory material in a straight configuration (FIG. 4A)and in a complex configuration having a spiral end and a compressionspring (FIG. 4B).

[0028] FIGS. 5A-E are partial cross-sectional views of a blood vessel inwhich a second embodiment of the intravascular device is being deployedand operated to stretch the blood vessel, using an integral compressionspring to push an anchored stretching wire away from an anchor wire.

[0029]FIG. 6 is a side view of one embodiment of the intravascularstretching device, which includes two stents and an integral compressionspring, which comprises a shape memory material, shown in a compressedconfiguration (FIG. 6A) and in an expanded configuration (FIG. 6B).

[0030]FIG. 7 is a side view of a stent and its integral compressionspring, which form part of one embodiment of the intravascularstretching device.

[0031]FIG. 8 is a side or plan view of a one embodiment of theintravascular stretching device, which includes two stents and anintegral compression spring shown in a compressed configuration (FIG.8A) and in a curvilinear expanded configuration (FIG. 8B).

DETAILED DESCRIPTION OF THE INVENTION

[0032] It is known that smooth muscle cells, which dominate the media,the major load bearing layer of the arterial wall, proliferate andincrease their production of extracellular matrix in response tomechanical stimulation. It was discovered that this knowledge could beadvantageously applied to create an autologous graft of appropriatediameter for coronary bypass or other vascular graft application usingan intravascular distension device to stimulate angiogenesis.

[0033] The distension device secures the donor blood vessel at differentpoints within the vessel and then distends or stretches the vesselbetween those points to form an elongated portion. The elongated portioncan then be excised for use as a vascular graft. The devices and methodsdescribed herein can used to make allogeneic and xenogeneic vasculargrafts, as well as the more preferred autogeneic vascular grafts.

[0034] The Devices and Methods of Operation

[0035] The device includes a stretching mechanism that can be attachedto and within a donor blood vessel, and a means for operating thestretching mechanism to cause the vessel to distend (i.e. extend), andan optional controller for controlling the operating means. At least twoanchoring points are needed to stretch the blood vessel. In preferredembodiments of the intravascular distention device and method, the axialforces for stretching the blood vessel are applied to at least oneelement of two or more elements, or portions thereof, that are secured(i.e. anchored) to the interior surface of the blood vessel to bestretched. These elements constitute the intravascular stretchingmechanism, and preferably can be delivered into the blood vessel by acatheter for installation and use.

[0036] The securing preferably is by frictional engagement, rather thanwith the use of other possible securing means such as adhesives orsutures. This engagement can be implemented with shape-changingmaterials, as detailed below, or with non-shape changing materials,which for example, may require balloon dilation to cause at least aportion of the stretching mechanism to expand and engage the interiorlumen portion of the blood vessel. As the secured elements are displacedfrom one another, the blood vessel segment therebetween experiencesaxial stretching forces.

[0037] In a first preferred embodiment, the intravascular stretchingmechanism includes a pair of wires, the end portions of which can beanchored within the blood vessel, and a means to displace the wires awayfrom each other and stretch the vessel. The blood vessel can bedisplaced (i.e. stretched) in rectilinearly, curvilinearly, or in acombination thereof. This displacement can be accomplished by any of avariety of techniques, for example, by mechanical, electromechanical, orhydraulic means.

[0038] In a second preferred embodiment, the intravascular stretchingmechanism comprises a pair of stents connected by a compression spring,which operates as a means to displace the stents away from each otherand stretch the vessel. As used herein, the term “stent” refers to anelastic, expandable, generally cylindrical anchor capable of engaging ablood vessel wall and resisting axial forces; it may or may not bestructurally like a conventional stent, which primarily serves to resistradial forces.

[0039] It is possible that components of these two different designs canbe combined, for example, using a combination of stents and wires toperform the stretching process. It is also envisioned that theseanchoring elements can take the form of other suitable structures nowknown or later developed, as the choice of anchoring elements generallycan be considered a matter of design choice.

[0040] A. Design Utilizing Anchored Wires

[0041] In some embodiments, the device employs two wires anchored withinthe blood vessel to be stretched. Examples of these are shown in FIGS.1-5 and described below.

The Device and Components Thereof

[0042] As shown in FIG. 1, a kit 10 includes a multi-lumen catheter 12and at least two wires: a stretching wire 14 a and an anchor wire 14 b.The catheter 12 has proximal end 16 and opposed distal end 18, and hasfour lumens, 17 a, 17 b, 17 c, and 17 d.

[0043] The catheter and wires can be provided as a kit or an assembleddevice. The catheter can be a standard, commercially available catheter.The catheter preferably has at least two lumens, one for each of the twowires. Additional lumens can be included for cold saline or otherpurposes. Selection of the appropriate diameter and length for thecatheter will of course depend on the particular blood vessel selectedfor stretching, as well as on the diameter and number of the anchorwires and stretching wires to be used.

[0044] The stretching wire 14 a has proximal end portion 20 a and distalend portion 22 a, and the anchor wire 14 b has proximal end portion 20 band distal end portion 22 b. Both the stretching wire and the anchorwire must be able to be secured to the interior surface of the bloodvessel to be stretched. FIGS. 2A and 2B illustrate a wire 14 that canserve as the anchor wire, the stretching wire, or both. Wire 14 has aproximal end portion 20 and a distal end portion 22. Distal end portion22 must be changeable from a straight configuration (FIG. 2A) into asecond configuration that will frictionally engage the interior surfaceof the blood vessel. In a preferred embodiment, the second configurationis a spiral, as shown in FIG. 2B. As used herein, the term “spiral”includes any helical, spiral, coiled, cylindrical, or curled shape.

[0045] The stretching wire 14 a should be of a suitable gauge andmaterial of construction so that it is resistant to buckling whensubjected to the pushing (stretching) forces. This gauge andconstruction can be different from that of the anchor wire 14 b, whichundergoes a pulling, rather than pushing, force during vesselstretching.

[0046] In other embodiments, the stretching wire and/or anchor wiredeploy into other, more complex configurations. For example, thestretching wire can deploy (e.g., upon warming to body temperature) intoan anchoring spiral with a compression spring, as showing in FIGS. 4A-B.FIG. 4A shows a stretching wire 40, having proximal end 41 and distalend 42, in its straight configuration, for example, at a temperatureless than body temperature. FIG. 4B shows the stretching wire 40 withthe distal end portion 42 transformed into a compression spring 44portion and spiral anchor portion 46.

[0047] The wires can be fabricated using suitable materials and methodsto accomplish the transformation of shape shown. For example, the wirescan be maintained in a straight profile with a removable sleeve thatsnugly fits around the wire. Such a sleeve could simply be slid off thewire following insertion. The sleeve could be a separate component thatfits within the catheter lumen or the catheter itself could serve thesleeve function. The shape change of the wire could be due to a springaction inherent in the material of construction of the wire, such that,upon sleeve removal the wire changes into the curled configuration. Sucha transformation can occur because of the elastic restorative forcesnormally exhibited in most metals and polymeric materials, forces thatcould be made, by one skilled in the art, to straighten a curved wireformed from these materials.

[0048] In a preferred embodiment, this configuration-changing functionis accomplished by having the wire, or at least the distal end portionthereof, include a suitable shape memory material. Shape memorymaterials typically have two distinct shapes, and the transition betweenthese shapes can occur in response to various stimuli. A preferredtransition stimulus is a change in temperature. For example, distal end22 of wire 14 can designed to be straight at room temperature, e.g.,about 20° C., (FIG. 2A) and to form a spiral shape when warmed to humanbody temperature, e.g., about 37° C., or above (FIG. 2B). Othertransition temperatures can be utilized.

[0049] Nickel-titanium alloys (e.g., Ninitol) that exhibit super-elasticand shape-memory effects are particularly suitable. Other shape memoryalloys and shape memory polymeric materials also can be used. Forexample, such shape memory materials can be fabricated to change shapefrom straight to spiral as the wires warm to body temperature followingin vivo insertion. Examples of shape memory polymers and other shapememory materials are described, for example, in PCT WO 99/42528 to MIT;U.S. Pat. No. 6,160,084 to Langer et al.; and Shape Memory Materials,(Otsuka & Wayman, eds.), Cambridge University Press (Oct. 1999), whichare hereby incorporated by reference. Methods for forming or coatingwires with such materials are known to those skilled in the art.

[0050] In a preferred embodiment, the device is formed of abiodegradable shape memory polymer, such as described in U.S. Pat. No.6,160,084 to Langer et al. The specific polymer could be tailored todegrade following completion of the stretching procedure. A deviceformed of such materials preferably would not need to be removed beforevessel excision or grafting.

[0051] It is important to note that the “memory” of the shape memorymaterial of the compression spring is not limited to axial recovery..The shape memory material can take the form of complex curves (e.g.,S-shaped) during their expansion and recovery, thereby creating tortuouspaths for the axial blood vessel growth and reducing axialdifferentiation between the anchoring elements while increasing thearterial path between them. See, e.g., FIG. 8.

Operating Means and Controller

[0052] The linear movement of the wires can be driven by a wide varietyof forces and driver means known in the art. The movement also may beconducted using mechanical, electromechanical, hydraulic, or other meansknown for controllably pushing/pulling one structure relative to asecond structure. Some of these are described in, or can be adapted fromthose describe in, U.S. Pat. No. 6,322,553 to Vito, which is herebyincorporated by reference.

[0053] The device includes means to operate the stretching mechanism,preferably including a prime mover and electronic drivers for the primemover. The prime mover can be an electromechanical (active) device, suchas a linear motor that operates the stretching mechanism to push and/orpull the distal end of the stretching wire away from the distal end ofthe anchor wire. The operating means preferably is operably connected tothe proximal end of at least the stretching wire.

[0054] A rotary motor could also be used to generate the required linearmotion, using techniques known in the art. Alternatively, the primemover can operate hydraulically. An active device generally requiresinput over time. The prime mover also can be a passive device such as aspring or a combination of a spring and a damper, where storedmechanical energy is used to push and/or pull the anchored portions ofthe wires away from each other.

[0055] Linear or rotary piezo micro-motor devices (actuators) deliversmall step sizes, small forces, have relatively simple controlelectronics and inherent force overload protection. Suitable devices areavailable from a number of vendors, including Micro Pulse Systems, Inc.Parameters of the operating means include the force applied by thestretching mechanism, the rate and direction of movement of thestretching mechanism, the length of time that the stretching mechanismis operated, and the type of stretching applied (e.g., continuous,cyclical, or intermittent).

[0056] The controller controls the operating means. The controller caninclude a microprocessor that can be activated and programmed to controlthe stretching process. It preferably can be reprogrammed as needed tocontrol the stretching process, based, for example, on x-ray data orother indications of how the process is proceeding.

[0057] The mechanical or hydraulic stretching mechanism works to movethe wires apart slowly over a period of up to several weeks. In oneembodiment, the passive driver element may be used to provide apredetermined stretch over time. In another embodiment, the driver maybe programmed to operate autonomously, for example to provide a stretchof several centimeters over about one month. Alternatively, cyclicstretching of increasing peak and mean amplitude may be used. Usingpiezo actuators, activating the driver can produce incremental movementsof the mechanical or hydraulic stretching mechanism as small as a fewmicrons. The prime mover is designed to be force limited to precludeoverstretching the vessel. Force limitation is inherent if thepiezoelectric actuators are used in either embodiment and, in the caseof permanent magnetic motors, can be designed into the electronic drivercircuit.

Methods of Use

[0058] The catheter can be inserted using well-established techniquesfor catheter insertion. Briefly, a guide wire is inserted using aninsertion catheter and is steered to the target blood vessel, usually byusing fluoroscopic techniques. The catheter then slides over the guidewire so that its distal end is located in the lumen of the target bloodvessel. Insertion of the catheter is facilitated by its radio-opaquenature.

[0059] In the methods employing shape memory materials that can beactivated by a temperature change, the anchor wire and stretching wiretypically will need to be maintained at a temperature below bodytemperature until their distal ends are correctly positioned inside thetarget blood vessel lumen. Techniques for accomplishing this temperaturecontrol are well known to those skilled in the art. For example, chilledsaline can be flowed through one or more of the catheter lumens tomaintain the temperature of the wire that is inside a catheter lumenbelow the activation temperature.

[0060] The device described with reference to FIGS. 1 and 2 can beinstalled and operated as illustrated in FIGS. 3A-E. In these Figures,blood flow should be from left (proximal) to right (distal). FIG. 3Ashows a catheter 12 in an inserted position within target blood vessel30, such that distal end 18 of catheter 12 is in the desired positionfor deployment of the stretching wire. As stretching wire 14 a isdeployed, its distal end portion 22 a warms to body temperature andchanges to a spiral, expanded configuration and engagescircumferentially the interior surface 31 of blood vessel 30, as shownin FIG. 3B. This engagement causes the stretching wire 14 a to besecured to the blood vessel 30 and establishes a distal anchoring pointtherein.

[0061] Next, a proximal anchoring point is established. As shown in FIG.3C, the catheter is first moved proximally (to the left) such thatdistal end 18 of catheter 12 is in the desired position for deploymentof the anchor wire. As anchor wire 14 b is deployed, its distal endportion 22 b warms to body temperature and changes to a spiral, expandedconfiguration and engages circumferentially the interior surface 32 ofblood vessel 30, as shown in FIG. 3D. This engagement causes the anchorwire 14 b to be secured to the blood vessel 30 and establishes aproximal anchoring point therein. These distal and proximal anchoringpoints, at surfaces 31 and 32, respectively, establish the blood vesselsegment to be stretched.

[0062] Stretching forces are then applied to one or both of the wires 14a and 14 b. Production and control of these stretching forces can beprovided as described above. Stretching can be continuous, cyclical, orintermittent, or in a combination thereof. FIG. 3E illustrates that thestretching wire 14 a has been pushed and caused the blood vessel 30 tobe stretched and grown between points 31 and 32. While the stretchingshown in FIG. 3E is linear (or rectilinear), stretching also can occurin curvilinear manner or in a combination of rectilinear and curvilinearstretching.

[0063] The device described with reference to FIGS. 1 and 3 can beinstalled and operated as illustrated in FIGS. 5A-E. In these Figures,blood flow should be from left (proximal) to right (distal). FIG. 5Ashows a catheter 12 in an inserted position within target blood vessel30, such that distal end 18 of catheter 12 is in the desired positionfor deployment of the stretching wire. As stretching wire 40 ispartially deployed, the tip end portion of distal end portion 42 warmsto body temperature and changes to a spiral, expanded configuration,forming a spiral 46 which engages circumferentially the interior surface31 of blood vessel 30, as shown in FIG. 5B. This engagement causes thestretching wire 14 a to be secured to the blood vessel 30 andestablishes a distal anchoring point therein.

[0064] As stretching wire 40 continues to be deployed, an intermediaryportion of the distal end portion 42 transforms into a helicalconfiguration operable as a compression spring 44, as shown in FIG. 5C.This compression spring 44 has an outer diameter that is smaller thanthat of the spiral 46, so that the compression spring 44 does notfrictionally engage and become anchored to the blood vessel wall.

[0065] After the compression spring 44 is fully formed, a proximalanchoring point is established. As shown in FIG. 5D, the catheter isfirst moved proximally (to the left) such that distal end 18 of catheter12 is in the desired position for deployment of the anchor wire. Asanchor wire 50 is deployed, its distal end portion 52 warms to bodytemperature and changes to a spiral, expanded configuration and engagescircumferentially the interior surface 32 of blood vessel 30, as shownin FIG. 3D. This engagement causes the anchor wire 50 to be secured tothe blood vessel 30 and establishes a proximal anchoring point therein.

[0066] These distal and proximal anchoring points, at surfaces 31 and32, respectively, establish the blood vessel segment to be stretched.Stretching forces are then applied by the release of compression inspring 44, which stretches the blood vessel 30 as shown in FIG. 5E. Itmay be convenient in this embodiment to simply leave the catheter inplace while stretching occurs.

[0067] B. Design Utilizing Combination of Stents and Springs

[0068] In another embodiment, the intravascular stretching meanscomprises a pair of stents, wherein the stents, rather than the wirespirals described above, function as the anchoring elements. While avariety of stent designs are commercially available or otherwise knownfor use in maintaining blood vessel diameter, the stents of the presentmethods and devices are designed and used to impart axial forces toincrease the length of the vessel.

The Device and Components Thereof

[0069] One example of such a design is illustrated in FIGS. 6A-B. FIGS.6A and 6B show intravascular device 60, which is comprised of a proximalstent 62, a distal stent 64, and a compression spring 66 secured betweenthe distal and proximal stents. One end of the proximal stent 62 isconnected to, or integral with, the proximal end 68 a of compressionspring 66, and one end of the distal stent 64 is connected to, orintegral with, the distal end 68 b of compression spring 66. FIG. 6Ashows device 60 with spring 66 in its compressed configuration, and FIG.6B shows device 60 with spring 66 in its expanded, or stretched,configuration.

[0070] Essentially any stent suitable for vascular implantation can beadapted for use in the present intravascular device. The stentpreferably is self-expanding, but also can deployable by other means(e.g., balloon dilation). The stent can be of various types, includingbut not limited to coil, mesh, and porous structures. One example of anexpandable stent is described in U.S. Pat. No. 6,033,436 to Steinke, etal. FIG. 7 shows one embodiment of a proximal or distal stent 70, whichis integral with compression spring 72 (only partially shown). Thisanchoring stent 70 is the structural feature that positively engages thevessel wall (not shown). Numerous other designs are known in the art orcan be routinely adapted therefrom. Some configurations are described inU.S. Pat. No. 6,193,744 to Ehr et al. These patents are herebyincorporated by reference.

[0071] Preferably, each stent is between about 5 and 20 mm, morepreferably about 10 mm, in length. The diameter of the stent desirablyis selected for the particular donor vessel, the size of which can vary.

[0072] The compression spring can be integrally formed with the stents,or the compression spring can be welded or otherwise attached to thestents following fabrication of each component. Preferably, the entiredevice is fabricated in one piece, i.e. as a single, contiguousassembly.

[0073] The device should be formed of and/or coated with a biocompatiblematerial, as known in the art. Preferably, the compression spring ismade of or includes a shape memory material, as describe herein (e.g.,nickel-titanium alloys and shape memory polymers). The compressionspring can alternatively be made from non-shape memory materials (e.g.,titanium, stainless steel, or a biocompatible polymer). The stentspreferably are also fabricated from a shape memory material, but may bemade from a non-shape memory material, as describe herein.

Methods of Use

[0074] The intravascular device is inserted into the target (i.e. donor)blood vessel. Then, the stents are self-expanded (e.g., if they comprisea shape memory material) or are expanded with the use of an installationdevice, such as a balloon, using or adapting techniques known in theart. The expansion process causes each stent to become frictionallyengaged, and thus anchored, to a circumferential portion of the interiorsurface of the blood vessel. The stents are anchored in positions suchthat the spring therebetween is in compression. The spring thus exertsan axial, expansion force causing the section of blood vessel betweenthe anchor points to be stretched. The expansion of the compressionspring thus causes the length of that blood vessel section to lengthen.

[0075] FIGS. 8A-B illustrate one embodiment of a stent-type stretchingdevice 80 comprising stents 84 and 86 with compression spring 82 in acompressed configuration (FIG. 8A) and with the compression spring 82 inan expanded or stretched configuration (FIG. 8B). FIG. 8B illustrateshow a blood vessel could be stretched in a curvilinear manner to twicethe original length, L. A stent-type device also could expand to stretchin a linear (or rectilinear) manner or in combination of curvilinear andrectilinear motion.

[0076] C. Other Design Features

[0077] The methods and devices described herein optionally can includegrowth factors or other growth stimulating agents (e.g., hormones) tofurther enhance blood vessel growth. For example, such growthstimulating agents can be delivered to the blood vessel by impregnatingthe materials forming the wires, stents or other device components.Alternatively or additionally, the device components can be providedwith a suitable coating or reservoirs that can contain and controllablyrelease such agents during the extension process. Examples of growthfactors include vascular endothelial growth factor (VEGF), endothelialcell growth factor (ECGF), basic fibroblast growth factor (bFGF), andplatelet derived growth factor (PDGF). Biocompatible polymeric materialsfor controlled release that are known in the art for drug delivery (seee.g., U.S. Pat. No. 5,879,713 to Roth et al.) can be adapted for usewith the devices described herein. The devices and methods also can beused in combination with external electric, magnetic, or electromagneticfields applied as a growth stimulus. See e.g., U.S. Pat. No. 4,846,181to Miller.

[0078] The devices also can optionally include appropriate drugs (e.g.,therapeutic or prophylactic agents) impregnated into or coated tostructural components, for example to minimize infections, thrombosis,inflammatory reactions, scar tissue formation, adhesion formation,and/or other adverse tissue reactions. For example, where tissue growthis to be avoided, certain antifibrotic agents may be present, such as5-fluourouracil or mitomycin. The device may be more generally providedwith coatings that are antibiotic or anti-inflammatory.

[0079] The intravascular stretching device also can be designed to limitadhesion formation while installed in the blood vessel. For example, thewires, stents, compression springs, or other components can beimpregnated or coated with materials selected to reduce adhesionformation as known in the art. Examples of such coating materialsinclude, but are not limited to, parylene, polytetrafluoroethylene(e.g., TEFLON™) and chromium (e.g., ME-92™, Armoloy Corp.), which can beused to coat a variety of other metal and polymer substrates.

[0080] Application of the Distension Devices and Methods

[0081] The present devices and methods are useful for forming a vasculargraft by axially stretching (i.e. distending or extending) a donor bloodvessel to stimulate growth. This stretching can performed in vivo or invitro.

[0082] While an autologous graft is preferred, the devices and methodsdescribed herein also can be applied to an artery from another human orother animal, including transgenic animals genetically engineered tohave tissues that will not be rejected by humans. For example, adistended artery from a transgenic pig might be used to provide axenogeneic arterial graft in a human.

[0083] The devices and methods can be sized to stretch blood vessels(e.g., veins, arteries) of essentially any size and located in orexcised from a variety of sites in the body of the patient or donor oranimal. Preferred blood vessels include, but are not limited to, theinternal mammary arteries, the gastroepipolic artery, the gastricartery, the radial artery, the femoral artery, and the splenic artery.Other arteries and veins may also be suitable blood vessels for use withthe methods and devices.

[0084] In a preferred embodiment of the in vivo distension method, thestretching mechanism is inserted into a donor blood vessel, for exampleusing a catheter, and vessel distension effected over a period of time.Then the stretching mechanism is withdrawn, and a portion of the donorblood vessel section is surgically removed. The ends of the donor vesselcan then be sutured end to end to repair the donor vessel, as iscommonly done in vascular repair without complication. Some bloodvessels used for coronary bypass surgery, such as the gastroepipolic andradial arteries, can be removed with minimal morbidity such that repairis unnecessary. The removed blood vessel section is then ready for useas a graft in a patient in need thereof, who preferably is the samepatient supplying the donor vessel.

[0085] Grafts for coronary by-pass surgery are typically between about10 cm and 15 cm in length, whereas grafts for by-pass in the peripheralcirculation are typically about 25 cm or more in length. Those of skillin the art can readily optimize the rate of vessel distension.Distension rates can be linear or nonlinear, and may average, forexample, between about 5 and 10 mm/day.

[0086] The device can also be used for in vitro distension. Currently, ashort segment of blood vessel can be salvaged during conventional bypasssurgery and an in vitro organ culture or bioreactor system can be usedto grow sufficient graft tissue for a second surgery. Such surgeriesrepresent about 30% of all bypass operations. The methods and devicesdescribed herein can be adapted to work with such surgeries, to increasethe length of graft material and/or to reduce the required length of thesalvaged segment. Stretched blood vessels can be effectively preservedfor bypass surgery, for example, using known cryogenic or freeze-dryingtechniques.

[0087] In this method, a portion of a donor blood vessel (e.g., shorterthan that needed for a graft) is surgically excised from the patient inneed of the graft, and then the vessel portion is stretched over aperiod of time in vitro in a medium for cell growth, for example, as ina bioreactor. As used herein, the phrase “medium for cell growth”includes any in vitro system for facilitating cell division,extra-cellular matrix formation, and growth of vessel tissue. See, forexample, U.S. Pat. No. 5,899,936 to Goldstein; U.S. Pat. No. 5,879,875,to Wiggins, et al.; and U.S. Pat. No. 5,888,720 to Mitrani, whichdescribe techniques for organ and tissue culture which can be adapted tothe methods described herein. All or a portion of the distended vesselis then ready for use as a graft in the patient. Where the donor is therecipient of the graft, the result using either approach advantageouslyis a totally autologous, living vascular graft.

[0088] Modifications and variations of the present invention will beobvious to those of skill in the art from the foregoing detaileddescription. Such modifications and variations are intended to comewithin the scope of the following claims.

We claim:
 1. A device for axially distending a blood vessel to inducegrowth of the vessel comprising: an intravascular stretching mechanismattachable directly to an interior lumen portion of the blood vessel;and a means for operating the stretching mechanism to cause the vesselto distend axially.
 2. The device of claim 1, wherein the intravascularstretching mechanism comprises: an anchoring wire having a distal endportion; and a stretching wire having a distal end portion; wherein thedistal end portions are separately anchorable to the interior lumenportion at positions axially remote from one another.
 3. The device ofclaim 2, wherein the distal end portion of the anchoring wire, thedistal end portion of the stretching wire, or both, comprise a shapememory material.
 4. The device of claim 3, wherein the shape memorymaterial comprises a shape memory alloy or a shape memory polymer. 5.The device of claim 4, wherein the shape memory material comprises abiodegradable shape memory polymer.
 6. The device of claim 3, whereinthe distal end portion of the stretching wire changes, in response to achange in temperature effective to trigger a change in the shape memorymaterial, from a substantially straight form into a spiral configurationwhich frictionally engages a first position in the interior lumenportion of the blood vessel when located therein.
 7. The device of claim6, wherein the distal end portion of the anchoring wire changes, inresponse to a change in temperature effective to trigger a change in theshape memory material, from a substantially straight form into a spiralconfiguration which engages a second position in the interior lumenportion of the blood vessel when located therein.
 8. The device of claim6, wherein the stretching wire further comprises an intermediary portionwhich changes, in response to a change in temperature effective totrigger a change in the shape memory material, from a substantiallystraight form into a helical configuration, said helical configurationbeing operable as a compression spring.
 9. The device of claim 2,further comprising a catheter having at least two lumens extendingbetween a proximal end and a distal end, one of said at least two lumensbeing suitable for delivering the stretching wire into the interiorlumen portion of the blood vessel, and another of said at least twolumens being suitable for delivering the anchor wire into the interiorlumen portion of the blood vessel.
 10. The device of claim 1, whereinthe means for operating comprises a prime mover that is mechanically,electromechanically, or hydraulically driven.
 11. The device of claim 1,wherein the means for operating the stretching mechanism causes an axialstretching force to be applied to the vessel in a continuous manner. 12.The device of claim 1, wherein the means for operating the stretchingmechanism causes an axial stretching force to be applied to the vesselin an intermittent manner.
 13. The device of claim 1, wherein the meansfor operating the stretching mechanism causes an axial stretching forceto be applied to the vessel in a cyclical manner.
 14. The device ofclaim 1, further comprising a controller for controlling the means foroperating the stretching mechanism.
 15. The device of claim 1, whereinthe intravascular stretching mechanism comprises a first stent, a secondstent, and a compression spring operably connected to the first stentand the second stent, the first and second stents being separatelyanchorable to the interior lumen portion at positions axially remotefrom one another.
 16. The device of claim 15, wherein the first stent,the second stent, the compression spring, or a combination thereof,comprises a shape memory material.
 17. The device of claim 16, whereinthe shape memory material comprises a shape memory alloy or a shapememory polymer.
 18. The device of claim 16, wherein the shape memorymaterial comprises a biodegradable shape memory polymer.
 19. The deviceof claim 1, further comprising a therapeutic or prophylactic agent. 20.The device of claim 19, wherein the a therapeutic or prophylactic agentcomprises a growth stimulating agent which can be released in aneffective amount to enhance growth of the blood vessel.
 21. The deviceof claim 1, wherein all or a portion of the intravascular stretchingmechanism is radio-opaque.
 22. A method for distending a blood vessel ofa human or animal to induce blood vessel growth, comprising the steps:inserting into an interior lumen portion of a blood vessel thestretching mechanism of the device of claim 1; anchoring the stretchingmechanism to the interior lumen portion at at least two positionsaxially remote from one another; and operating the stretching mechanismto axially stretch the blood vessel between said at least two positionsover a period of time effective to induce axial growth of the bloodvessel.
 23. The method of claim 22, wherein the stretching occurs invivo.
 24. The method of claim 22, wherein the stretching occurs in vitroin a medium for cell growth.
 25. The method of claim 22, wherein thestretching mechanism is operated to apply an axial stretching force tothe vessel in a continuous manner.
 26. The method of claim 22, whereinthe stretching mechanism is operated to apply an axial stretching forceto the vessel in an intermittent manner.
 27. The method of claim 22,wherein the stretching mechanism is operated to apply an axialstretching force to the vessel in a cyclical manner.
 28. The method ofclaim 22, wherein the blood vessel is selected from the group consistingof an internal mammary artery, a femoral artery, a gastroepipolicartery, a gastric artery, a radial artery, and a splenic artery.
 29. Themethod of claim 22, wherein the intravascular stretching mechanismcomprises an anchoring wire having a distal end portion, and astretching wire having a distal end portion, wherein the distal endportions are separately anchorable to the interior lumen portion atpositions axially remote from one another.
 30. The method of claim 22,wherein the intravascular stretching mechanism comprises a first stent,a second stent, and a compression spring operably connected to the firststent and the second stent, the first and second stents being separatelyanchorable to the interior lumen portion at positions axially remotefrom one another.
 31. The method of claim 22, wherein the anchoring ofthe stretching mechanism comprises dilating a balloon to cause at leasta portion of the stretching mechanism to expand and engage the interiorlumen portion of the blood vessel.
 32. A method of forming a vasculargraft for a human or animal in need thereof, comprising: distending adonor blood vessel by use of the method of claim 22; and excising aportion of the distended donor vessel, said portion thereby providing avascular graft.
 33. The method of claim 32, wherein the vesseldistension is conducted in vivo.
 34. The method of claim 32, wherein thevessel distension is conducted in vitro in a medium for cell growth. 35.The method of claim 32, wherein the donor blood vessel is obtained froma human or transgenic animal.